Pattern transfer device for mass transfer of micro-patterns onto medical devices

ABSTRACT

This invention is directed to a pattern transfer device and assembly for mass-transfer/fabrication of micro-sized features/structures onto the inner diameter (ID) surface of a stent. This new approach is provided by technique of through mask electrical micro-machining. One embodiment discloses an application of electrical micro-machining to the ID of a stent using a customized electrode configured specifically for machining micro-sized features/structures.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.14/197,513, filed Mar. 5, 2014, which will issue as U.S. Pat. No.9,422,633 on Aug. 23, 2016; which is a continuation of U.S. patentapplication Ser. No. 13/663,808, filed Oct. 30, 2012, now U.S. Pat. No.8,668,818, issued on Mar. 11, 2014; which is a continuation of U.S.patent application Ser. No. 12/914,467, filed on Oct. 28, 2010, now U.S.Pat. No. 8,329,021 issued on Dec. 11, 2012, all herein incorporated intheir entireties.

BACKGROUND OF THE INVENTION

This invention generally relates to therapeutic tissue engineeringdevices for the treatment of Ischemic Diseases. More specifically, thepresent application relates to a process of electrochemically machiningmicro-sized micro-pattern structures onto the inner diameter of aBalloon eXpanding (Bx) or Self eXpanding (Sx) stent.

Alternative techniques that may be employed to fabricate micro-sizedfeatures on the inner diameters of medical devices include direct laserablation, metal stamping/pressing, and photolithography/wet etching. Itis believed that none of these techniques have the potential for useeither in part or entirely in the fore-mentioned process to accomplishmicro-sized features on the inner diameter of the medical device. Thepresent invention solves these problems as well as others.

SUMMARY OF THE INVENTION

Provided herein are methods and systems for mass-transfer/fabrication ofmicro-sized features/structures onto the inner diameter surface of astent. The method of producing micro-patterns on a medical devicegenerally comprises providing a metal electrode cathode, anon-conducting mask coating the outer diameter of the metal electrodeand a medical device anode; attaining the non-conducting mask by coatingthe metal electrode cathode; patterning desired features on the mask andthen transferring the desired features to the medical device anode byelectrochemical micromachining. In one embodiment, this method involvesthe use of an electrode/non-conducing mask/stent assembly.

The methods and systems are set forth in part in the description whichfollows, and in part will be obvious from the description, or can belearned by practice of the methods, compositions, and systems. In oneembodiment, the new approach is provided by technique of through maskelectrochemical micro-machining. The present application discloses anapplication of electrochemical micro-machining to the inner diameter ofa stent using a customized electrode configured specifically formachining micro-sized features/structures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a partial cross-sectional perspective view of a portion of aintravascular stent embedded within an arterial wall of a patient;

FIG. 2 is an exploded view of the outlined portion of FIG. 1 denoted asFIG. 2;

FIG. 3 is a partial cross-sectional, perspective view corresponding toFIG. 1 after the passage of time;

FIG. 4 is an exploded view of the outlined portion of FIG. 3 denoted asFIG. 4;

FIG. 5 is a partial cross-sectional view of the stent and artery ofFIGS. 1 and 3 after a further passage of time;

FIG. 6 is an exploded view of the outlined portion of FIG. 5 denoted asFIG. 6;

FIG. 7 is a partial cross-sectional view of the stent and artery of FIG.5, taken along lines 7-7 of FIG. 5, and illustrates rapidendothelialization resulting in a thin neointimal layer covering thestent;

FIG. 8A is a side elevational view of an intravascular stent;

FIG. 8B is an enlarged perspective view of a portion of theintravascular stent of FIG. 8A;

FIG. 9 is a perspective view of the micro-patterned electrode-implantconfiguration for electrochemical micromachining;

FIGS. 10-14 are various embodiments of an exploded view of amicro-pattern, illustrating various cross-sectional configurations andcharacteristics of various embodiments of the micro-pattern inaccordance with one embodiment;

FIG. 15 is an enlarged perspective view of the end section of themicro-patterned electrode-stent configuration for electrochemicalmicro-machining, showing the stent/implant (+), patternedpolymer/Non-conducting mask, and the metal electrode (−);

FIG. 16 is a perspective view of the middle section of themicro-patterned electrode-implant configuration for electrochemicalmicro-machining;

FIG. 17 is an enlarged perspective view of the micro-patternedstent/implant post electrochemical micromachining;

FIG. 18 is an enlarged perspective view of the micro-patterned patternoriented in the circumferential direction with an electrode polymerthickness of about 25-40 μm;

FIG. 19 is a photomicrograph at low magnification of the micro-patternstructure machined onto the inner diameter of the stent viaelectrochemical micro-machining;

FIG. 20 is a photomicrograph at low magnification of the micro-patternstructure at a joint of the stent machined onto the inner diameter ofthe stent via electrochemical micro-machining;

FIG. 21 is an electron image of the micro-pattern structures on thestent machined onto the inner diameter of the stent via electrochemicalmicro-machining.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The foregoing and other features and advantages of the invention areapparent from the following detailed description of exemplaryembodiments, read in conjunction with the accompanying drawings. Thedetailed description and drawings are merely illustrative of theinvention rather than limiting, the scope of the invention being definedby the appended claims and equivalents thereof.

With reference to FIGS. 1 and 2, an intravascular stent 200 isillustrated being disposed within an artery 290 in engagement witharterial wall 210. For illustrative purposes only, intravascular stent200, shown in FIGS. 1-6 is a Palmaz™ balloon-expandable stent, as isknown in the art, stent 200 having an inner diameter 201 and an outerdiameter 202. FIGS. 1 and 2 illustrate stent 200 shortly after it hasbeen placed within artery 290, and after stent 200 has been embeddedinto arterial wall 210, as is known in the art. FIGS. 1 and 2 illustratewhat may be generally characterized as correct placement of anintravascular stent. Stent 200 preferably includes a plurality of metalmembers, or struts, 203, which may be manufactured of stainless steel,or other metal materials, as is known in the art. As illustrated inFIGS. 1 and 2, correct placement of stent 200 results in tissue mounds211 protruding between the struts 203, after struts 203 have beenembedded in the arterial wall 210. Struts 203 also form troughs, orlinear depressions, 204 in arterial wall 210. Dependent upon the degreeof blockage of artery 290, and the type and amount of instrumentationutilized prior to placement of stent 200, the mounds of tissue 211 mayretain endothelial cells (not shown). machined pattern may includefeatures which pin or demote cell proliferation. These patterns may beused to steer cells to control a directionality of healing response. Anytype of cell is encompassed by the present invention, which have acellular membrane. Most distinct cell types arise from a singletotipotent cell that differentiates into hundreds of different celltypes during the course of development. Multicellular organisms arecomposed of cells that fall into two fundamental types: germ cells andsomatic cells. During development, somatic cells will become morespecialized and form the three primary germ layers: ectoderm, mesoderm,and endoderm. After formation of the three germ layers, cells willcontinue to specialize until they reach a terminally differentiatedstate that is much more resistant to changes in cell type than itsprogenitors. The ectoderm differentiates to form the nervous system(spine, peripheral nerves and brain), tooth enamel and the epidermis(the outer part of integument). It also forms the lining of mouth, anus,nostrils, sweat glands, hair and nails. The endoderm forms thegastrointestinal tract cells, the respiratory tract cells, the endocrineglands and organ cells, the auditory system cells, and the urinarysystem cells. The mesoderm forms mesenchyme (connective tissue),mesothelium, non-epithelial blood cells and coelomocytes. Mesotheliumlines coeloms; forms the muscles, septa (cross-wise partitions) andmesenteries (length-wise partitions); and forms part of the gonads (therest being the gametes).

Alternative medical devices may be employed with the grooves disclosedherein, such as grafts, filters, implants, temporary implants such as avena cava filter or an insulin pump needle, bone grafts, dentalimplants, heart valves or electrical leads, temporary tubing, or anyother device where grooves may be needed or cell growth is required.

With reference to FIGS. 3 and 4, after the passage of time, a thin layerof thrombus 215 rapidly fills the depressions 204, and covers the innerdiameters 201 of stent 200. As seen in FIG. 4, the edges 216 of thrombus215 feather toward the tissue mounds 211 protruding between the struts203. The endothelial cells which were retained on tissue mounds 211 canprovide for reendothelialization of arterial wall 210.

With reference to FIGS. 5 and 6, endothelial regeneration of artery wall210 proceeds in a multicentric fashion, as illustrated by arrows 217,with the endothelial cells migrating to, and over, the struts 203 ofstent 200 covered by thrombus 215. Assuming that the stent 200 has beenproperly implanted, or placed, as illustrated in FIGS. 1 and 2, thesatisfactory, rapid endothelialization results in a thin tissue layer218, as shown in FIG. 7. As is known in the art, to attain properplacement, or embedding, of stent 200, stent 200 must be slightlyoverexpanded. In the case of stent 200, which is a balloon-expandablestent, the balloon diameter chosen for the final expansion of stent 200must be 10% to 15% larger than the matched diameter of the artery, orvessel, adjacent the site of implantation. As shown in FIG. 7, thediameter Di of the lumen 219 of artery 290 is satisfactory. If thereendothelialization of artery wall 210 is impaired by underexpansion ofthe stent or by excessive denudation of the arterial wall prior to, orduring, stent placement, slower reendothelialization occurs. Thisresults in increased thrombus deposition, proliferation of muscle cells,and a decreased luminal diameter Di, due to the formation of a thickerneointimal layer.

With reference to FIGS. 8A and 8B, an intravascular stent 300 inaccordance with one embodiment is illustrated. For illustrative purposesonly, the structure of intravascular stent 300 is illustrated as being aPalmaz™ balloon-expandable stent, as is known in the art, illustrated inits initial, unexpanded configuration. It should be understood that theimprovement of the embodiments disclosed herein is believed to besuitable for use with any intravascular stent having any construction ormade of any material as will be hereinafter described. Similarly, theimprovement of the embodiments disclosed herein in methods formanufacturing intravascular stents is also believed to be applicable tothe manufacturing of any type of intravascular stent as will also behereinafter described.

In one embodiment, the intravascular stent 300 consists generally of atubular cylindrical element having a stent wall that defines an innerdiameter 301 and an outer diameter 302 of the stent. As shown in FIGS.8A and 8B, a plurality of first structural elements 310 are arrayedabout the circumferential axis 314 of the stent 300 and extend generallyparallel along the longitudinal axis 316 of the stent 300. A pluralityof second structural elements 312 are oriented generally parallel to thecircumferential axis 314 of the stent 300 and interconnect adjacentpairs of the plurality of first structural elements 310. Each of theplurality of second structural elements 312 have a generally sinusoidalconfiguration with at least one complete sine curve, i.e., having bothpositive and negative amplitude in the proximal and distal directionsrelative to the longitudinal axis 316 of the intravascular stent 300,being subtended between adjacent pairs of the first structural elements310. A plurality of peaks 312 a and a plurality of troughs 312 b areformed in each the second structural elements 312. The plurality ofpeaks 312 a and the plurality of troughs 312 b may have either regularor irregular periodicity along the longitudinal axis of each of theplurality of second structural elements 312 or each of the plurality ofsecond structural elements 312 may have regions of regular periodicityand regions of irregular periodicity. A plurality of flex regions 318are formed in each of the plurality of first structural members 310.Each of the plurality of flex regions 318 are formed as narrowed regionsof the first structural element 310 and may have a V-shaped orsinusoidal configuration (shown in FIGS. 15 and 16) which projectcircumferentially from each of the plurality of first structuralelements 310. It is contemplated that one of the plurality of flexregions 318 may be positioned intermediate adjacent pairs of the secondstructural elements 312 along the first structural element 310.

The plurality of first structural elements 310 and the plurality ofsecond structural elements 312 are preferably made of materials selectedfrom the group consisting of elemental titanium, vanadium, aluminum,nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium,niobium, scandium, platinum, cobalt, palladium, manganese, molybdenumand alloys thereof, and nitinol and stainless steel. The plurality offirst structural elements 310 and the plurality of second structuralelements 312 may be made of the same material or of different materialsand have the same material properties or have different materialproperties. The term material properties is intended to encompassphysical properties, including, for example and not by way oflimitation, elasticity, tensile strength, mechanical properties,hardness, bulk and/or surface grain size, grain composition, grainboundary size, and intra- and inter-granular precipitates. Similarly,the materials selected for the plurality of first structural elements310 and the plurality of second structural elements 312 may be selectedto have the same or different chemical properties. The term materialproperties is intended to encompass both any chemical reaction andchange of state that the material may undergo after being implanted intoa body and the physiological response of the body to the material afterimplantation.

As illustrated in FIG. 8A, intravascular stent, or stent, 300 has aninner diameter 301, and an outer diameter 302, outer diameter 302normally being embedded into arterial wall 210 in an abuttingrelationship. In accordance with one embodiment, the inner diameter 301of stent 300 is provided with a micro-pattern 400 (shown in FIG. 9). Themicro-pattern 400 of one embodiment may be provided in, or on, the innerdiameter or abluminal surface 301 of stent 300 by mass transferring themicro-pattern(s) via through-mask electrochemical micro-machining(ECμM), as will be hereinafter described in greater detail. Forillustrative purposes only, the micro-pattern is shown in FIGS. 9-21 asa plurality of linearly grooved structures. It should be understood thatthe micro-pattern can be provided in a wide array of shapes, structures,and patterns, such as, for example, and not by way of limitation, a wavestructure, cross-hatched pattern, or concentric circles, as describedmore fully below. Stents generally have an inner diameter or abluminalsurface and an outer diameter or luminal surface, i.e. the surface thatcontacts a lumen, blood vessel, cavity, and the like.

As shown in FIG. 9, the micro-pattern 400 may be disposed with itslongitudinal axis being disposed substantially parallel with thelongitudinal axis 316 of stent 300, in accordance with one embodiment.Alternatively, the longitudinal axis of the micro-pattern 400 may bedisposed substantially perpendicular to the longitudinal axis 316 ofstent 300, as shown in FIG. 18; or the longitudinal axis of themicro-pattern may be disposed at an obtuse, or acute, angle with respectto the longitudinal axis 316 of stent 300. The angle that micro-pattern400 makes with respect to longitudinal axis 316 is either an acute or anobtuse angle dependent upon from which direction the angle is measuredwith respect to the longitudinal axis 316 of stent 300. The selection ofthe angle of the micro-pattern 400 with respect to the longitudinal axis316 may be selected according to the placement of medical device 300,type of endothelial cell, and/or direction of growth for the endothelialcell.

A plurality of micro-patterns 400 may be disposed on the inner diameter301 of stent 300. The plurality of micro-patterns could be provided in aserpentine fashion or in a cross-hatched manner. It should be noted thatthe angular disposition and location of the plurality of micro-patterns400 will vary and be altered upon the expansion of stent 300 within theartery 290 (FIG. 1), and the stent 300 being illustrated in itsunexpanded configuration in FIG. 9. It should be further noted, aspreviously discussed, that the mass transfer of the micro-pattern, ormicro-patterns, may be provided in, or on, the inner diameter of anyintravascular stent, so as to increase the rate of migration ofendothelial cells on, and over, the inner diameter of the intravascularstent.

In general, micro-pattern 400 has a width W, a depth D, and a length L.The width W and depth D may be the same, and not vary, along the lengthL of the micro-pattern 400. Alternatively, the width W of themicro-pattern may vary along the length L of the micro-pattern 400.Alternatively, the depth D of the micro-pattern may vary along thelength L. Alternatively, both the width W and the depth D of themicro-pattern 400 may vary along the length L. Similarly, as with thelocation and angular disposition of micro-pattern, or micro-patterns,400 as described in connection with FIG. 9, the width W, depth D, andlength L of the micro-pattern, or micro-patterns, 400 can vary asdesired, and different types of micro-patterns 400 could be disposed onthe inner diameter 301 of stent 300.

As desired, the cross-sectional configuration of the micro-pattern, ormicro-patterns, 400 may vary along the length L of the micro-pattern(s);or the cross-sectional configuration of the micro-pattern may not varyalong the length. The cross-sectional configuration of themicro-pattern, or micro-patterns, 400 may be substantially symmetricalabout the longitudinal axis 410 of micro-pattern 400; or thecross-sectional configuration of the at least one micro-pattern may besubstantially asymmetrical about the longitudinal axis 410. Thecross-sectional configurations of micro-pattern 400 can assume a varietyof shapes, and include those cross-sectional configurations which aresubstantially: square shaped (FIG. 10); U shaped (FIG. 11); triangular,or V shaped (FIG. 12); rectangular shape (FIG. 13); and triangular, orkeyway shaped (FIG. 14). The wall surface 303 of each micro-pattern 400may be substantially smooth.

The depth D of micro-pattern, or micro-patterns, 400 may fall within arange of approximately one-half to approximately ten microns. However,in no event should the depth D of micro-pattern, or micro-patterns, 400exceed the distance between the inner diameter 301 and the outerdiameter 302 of the stent 300. The width W of micro-pattern, ormicro-patterns, 400, may fall within a range of approximately two toapproximately forty microns. Of course, the width W and depth D could bevaried from the foregoing ranges, provided the rate of migration ofendothelial cells onto stent 300 is not impaired. The length L ofmicro-pattern 400 may extend the entire length of stent 300, such asmicro-pattern 400 of FIG. 9; or the length L′ of a micro-pattern may beless than the entire length of stent 300, such as micro-pattern 400 inFIG. 18. The micro-pattern, or micro-patterns, may be continuous, ordiscontinuous, along the length of the inner diameter 301 of stent 300.

The portion of the inner diameter 301 of stent 300 which has not beenprovided with a micro-pattern, or micro-patterns, 400 in accordance withone embodiment, may have any suitable, or desired, surface finish, suchas an electropolished surface, as is known in the art, or may beprovided with whatever surface finish or coating is desired. It isbelieved that when a micro-pattern 400 in accordance with one embodimentis disposed, or provided, on, or in, the inner diameter 301 of anintravascular stent 300, after the implantation of stent 300, the rateof migration of endothelial cells upon the inner diameter 301 of stent300 will be increased over that rate of migration which would beobtained if the inner diameter 301 were not provided with amicro-pattern 400 in accordance with one embodiment.

To manufacture intravascular stents with a mass-transferredmicro-pattern disposed in the inner diameter of the stent, oneembodiment provides a method for mass transferring the micro-patternonto the inner diameter of an intravascular stent via through-mask ECμM.

With reference to FIG. 9, the configuration of the micro-patternedintravascular stent/electrode through-mask ECμM assembly 402 comprises ametal electrode 380, a non-conducting mask 340 disposed on the outerdiameter 360 of the electrode 380, and an intravascular stent/implant300. The micro-patterned masked electrode/intravascular stentconfiguration for the through-mask ECμM process is also shown in FIGS.16, and 18. The configurations shown in FIGS. 15 and 16 illustrate amasked electrode 350, oriented parallel to the longitudinal axis 316 ofthe stent 300, having a micro-pattern 400 that is also parallel to thelongitudinal axis 316 of the intravascular stent 300. The configurationshown in FIG. 18 shows the masked electrode 350, oriented parallel tothe longitudinal axis 316 of the stent 300, having a micro-pattern 400that is perpendicular to the longitudinal axis 316 of the intravascularstent 300.

As shown in FIG. 15, the through-mask ECμM process involves firstattaining a masked-electrode 350 by coating an outer diameter 360 of ametal electrode 380 with a non-conducting mask 340, imparting amicro-pattern 400 on the outer diameter of the masked-electrode 350 vialaser ablation or other techniques, mounting the intravascular stent 300over the micro-patterned masked electrode 350, such that the innerdiameter 301 of the stent 300 is in contact with the micro-patternedmasked electrode 350, and then mass-transferring the micro-pattern 400features on the outer diameter of the masked-electrode 350 onto theinner diameter 301 of the intravascular stent/implant 300 viathrough-mask ECμM 402. During the machining process, direct or pulsedcurrents, voltages and/or a combination thereof, are applied for aspecified amount of time or charge before the assembly is removed fromthe electrolyte solution, washed and dried. Then, the intravascularstent 300 is removed from the masked electrode 350 and, upon inspection;the inner diameter 301 of the stent 300 will display a micro-pattern400, as shown in FIGS. 17, 19, and 20.

The displayed micro-pattern features on the inner diameter 301 of theintravascular stent 300 is a result of micro-machining throughdistinctly defined channels of electrical current such that when apotential is applied between the masked electrode 350 and the innerdiameter 301 of the stent 300, only those areas exposed to these currentchannels will undergo oxidative processes M0(s)+electrons−>M+(aq). Thedefined channels are essentially the conductive pathways through whichdissolution will take place. The channel bounded on one side by themasked electrode 350 and on the other side by the inner diameter 301 ofthe stent 300 defines the “machining gap” as used herein. The size ofthe machining gap is largely a function of the feature size(s) impartedon the patterned electrode and thus, can vary from application toapplication. For example, the working relationships for machiningmicro-sized micro-patterns that are relatively shallow to promoteendothelial function may be different from larger features designed toload therapeutic agents. Machining is rendered exclusive to only thosesurfaces of the intravascular stent 300 most proximal to the electrode380, in-turn rendering the distal surfaces 302 of the stent 300, whichessentially see insufficient current densities to initiate activedissolution, passive (no dissolution) during the machining process. Ingeneral, the dimensional attributes of all machining gaps, electrodepattern, target pattern on implant etc., are likely to be within thesame order of magnitude of each other. A regime of machining parametersmay be selected to be coupled with the construction of thestent/electrode assembly to allow for the active machining to occur atsites most proximal to the counter electrode surface, which would bethough the machining gap.

Rate of Machining is the rate at which different metals can be machineddepends on the amount of current passed and the duration for which it ispassed. The interelectrode distance (machining gap) will have some playin the electrical current distribution and thus, may affect themachining rate to some extent.

Pulsed current in Electrochemical machining conventionally utilizes DCinput as power source. Alternative techniques however employ highfrequency pulsed voltage to reach better resolutions. The appliedvoltage waveform plays a crucial role in defining a profile quality andsurface finish of microECM'ed part. With the use of ultrahigh frequencyinputs around GHz range, electrochemical reactions are restricted toelectrode regions in close proximity which exceeds far beyond the 0.1 mmlimited spatial resolution defined solely by electrolytic currentdensity in DC voltages. Machining is performed during pulse-on time andpulse-off time is kept long enough to dissipate heated electrolyte andproduced gas formed during pulse-on time. With higher frequencies, themachined cavity diameter converges to the tool diameter. On the otherhand, increased amplitude would increase the removed material for agiven time, since more electrons are driven with more power supplied.

Although the material removal rate may be dictated by the reaction rate,the flushing away of the reaction products from the machining zone isalso important for efficient machining. The selection of the ideal flowpatterns and velocity was paramount for obtaining the best results. Thegradient in the flow path directly affected the surface finish and depthof cut. The ability to transfer micro-sized features onto the ID of thestent was achieved via a simple immersion of the stent/electrodeassembly into the electrolyte with gentle stirring of peripheralelectrolyte. A more forced agitation within the machining gap may beemployed in other embodiments.

MicroECM setups mostly have actuation mechanisms for repeatablemachining. Two types of actuation are possible on a setup and theydefine types of control mechanisms as well: open-loop and closed-loopcontrols. The positioning system may be either open or closed loop.

The metal electrode 380, which can be made from components of stainlesssteel, brass, copper, graphite, molybdenum, silver, tungsten, platinum,etc., is coated or modified to render its outer diameter 360electrically non-conductive. This can be accomplished by coating theouter diameter 360 of the metal electrode 380 with a polymer, ceramic,oxide or any other electrically non-conductive material. Polymers of,for example, and not by way of limitation, phenol and its derivatives,phenylenediamines, and overoxidized or electroinactive polypyrrole canbe used as the non-conductive coating material. The coating process canbe carried out by dipping, spray coating, air brush, lamination or otherchemical or physical vapor deposition techniques.

This non-conducting layer 340, with a thickness ranging from hundreds ofangstrom up to microns, preferably the thickness is between about 25 μmto 40 μm, is then patterned before the inner diameter 301 of theintravascular stent 300 is machined. The thickness of the non-conductivelayer 340 can be optimized, by inspection or measurement, during thecoating process for a specific material/apparatus combination. Thepatterning can be done via laser ablation, particularly using anultra-short pulsed femto-second laser, or other techniques with thecapability to achieve the electrode pattern having desired dimensions.

The laser ablation technique involves ablating the non-conducting maskmaterial 340 such that a desired pattern is formed on themasked-electrode 350. A wide variety of laser systems can be used—frommicrosecond pulsed infrared CO₂ gas lasers at wavelengths between 9.3-11μm to femto- to nanosecond pulsed excimer gas lasers in the 157-353 nmUV wavelength range (i.e., the nanosecond Argon fluoride (ArF) excimerlaser systems, the nanosecond Xenon chloride (XeCl) excimer lasersystems, or the femtoseond krypton fluoride (KrF) excimer laser systems)and femto- to nanosecond pulsed solid state lasers between wavelengthsof 266-1060 nm (i.e. the nanoseond Er:YAG lasers in the mid-infraredwavelength region).

In one embodiment, a 1550 nm ultra-short pulse femto-second laser isemployed having an energy per pulse of about 50 μJ, plus about 5%, anaverage power of about 5 watts or 7.5 watts, a pulse width of less than1.0 ps, typically about 850 fs, a peak power greater than about 50 MW,and a repetition rate of about 100 kHz to about 150 kHz. The pulsefrequency used in laser ablation patterning varies with the solid-,liquid- or gas-state targets as they go through complex phasetransitions during the application of high electrical energy. The laserablation process employed has a repletion rate of 25 kHz, in oneembodiment; alternatively, the laser ablation process has a repletionrate between about 1 to 50 kHz. A pattern resolution of 1-2 μm withoutany undesired heat-affected zone is achievable. Thus, the laser has theability to ablate the mask material, leaving minimal to no heat effector recast (cold ablation) and thus, allows for the preservation ofdimensional features.

Cover gases may be used for patterning polymeric and ceramic based maskswith femto-second lasing methods include argon, helium, and mixtures ofthe two. The absence of heat effect and the need to subject the laserpatterned electrodes to subsequent finishing operations allow forquicker process turnaround times, better feature quality and dimensionalretention and the opportunity to scale feature dimensions down to singleto sub-micron scale. For femtosecond-, picosecond- andnanosecond-pulsing to be all applicable, chirped pulse amplificationtype(CPA) Ti-sapphire-based laser systems can be employed.

The micro-pattern 400 imparted on the masked electrode 350 should havefeature sizes commensurate to the thickness of the non-conducting layer340 for the layer to be machined properly. In general, the micro-pattern400 imparted on the masked electrode 350 has a width W, a depth D, and alength L. The width W and depth D may be the same, and not vary, alongthe length L of the micro-pattern 400. Alternatively, the width W of themicro-pattern 400 may vary along the length L of the micro-pattern 400.Alternatively, the depth D of the micro-pattern 400 may vary along thelength L of the micro-pattern 400. Alternatively, both the width W andthe depth D of the micro-pattern 400 may vary along the length of themicro-pattern 400. The cumulative outer diameter of the patternedelectrode 350 should be sized to ensure adequate contact between theintravascular stent 300 and the non-conducting mask 340 so thatelectrical current leakage between the contacting surfaces is minimal.The thickness of the non-conductive layer/mask 340 will measure on thesame order of the feature size to be transferred to the inner diameter301 of the stent 300. For example, a square-wave micro-pattern measuring12 microns wide and 2 microns deep, which repeats every 24 microns,employs a non-conducting layer thickness nearly identical to the patternfeature size, i.e. a 2 micron thick layer on the electrode. Alternativethicknesses of the non-conductive layer/mask 340 may be used, forexample, about 1-100 microns wide and/or 1-50 microns deep, which mayrepeat every 1-100 microns. The parameter will also vary with thespecific length scale of micro-pattern 400 to be mounted. Alternatively,nano-sized patterns on implant surfaces will therefore also usesimilarly dimensioned features machined into the electrode mask.

Once the masked electrode 350 has been patterned, the intravascularstent 300, usually made of stainless steel, is mounted onto the maskedelectrode 350, positioned, and placed into an electrolyte forelectrochemical micro-machining, as shown in FIG. 9. The intravascularstent may be made of any metal deemed biocompatible and eligible for useas Class I, II, or III medical device implants. For example, and not byway of limitation, the stent may be made of metal alloys of stainlesssteel, CoCr, Nitinol, MP35N, PtCr, or TaTi.

Through-mask ECμM 402 requires a better degree of tooling and processcontrol compared to the conventional ECM technique. Thus, the selectionof electrolyte is to be selected according to the extremely small gapbetween the tool and the workpiece. The masked electrode 350 and theinner diameter 301 of the stent 300 are circuited through theelectrolyte flowing from masked electrode 350 to the inner diameter 301of the stent 300. The electrolyte of choice should satisfy therequirements of being electrically conductive, being able to dissolvethe electrode and intravascular stent materials, and being renderedpassive in the absence of external power to drive the dissolutionprocess. When considering the electrolyte, the following attributes aretaken into account: water solvent based, neutral/acidic based, abilityto machine the implant material, processing temperature range andcapability, general electrode assembly with implant compatibility,whether reaction by-products are formed, and/or throwing power along andothers that either are directly influenced or strongly interact withthese mentioned.

In common micromachining processes, electrolytes have component(s) ofKCl, unsaturated AgCl, NaCl, LiCl, NaHCO₃, NaOH, saline, H₂SO₄, HF,H₃PO₄, or/and other appropriate preparations. Depending on theintravascular stent material, the electrolyte of choice may range fromconcentrated forms of acids to dilute mixtures of neutral salt. In oneembodiment, for example, the electrolyte used for implants made of a316LVM stainless steel and L-605 alloy is an 85% phosphoric acidsolution which has demonstrated useful ECM attributes and patterntransfer characteristics using a 1-5V regime at temperatures between20-50° C. In another embodiment, the electrolyte is a LiCl/ethanolmixture. The selection of the electrolyte is dictated by the material ofwhich the implant is made of.

Electrolytes for different alloys include the following: Iron-basedalloys may use chloride based solutions in water; Ni-based alloys mayuse HCl based solutions or mixtures of brine and H₂SO₄; Ti-based alloysmay use 10% HF+10% HCl+10% HNO₃ based solutions; Co—Cr—W-based alloysmay use NaCl based solutions; WC-based alloys may use strong alkalinesolutions; stainless steel and Co—Cr-based alloys may use phosphoric orchloride based solutions; and nitinol-based alloys may use sulfuric andLiCl based solutions. The electrolyte conductivity is dependent on anumber of parameters, including: starting electrode distance,concentration of salt in the solution, local hydroxide concentration inelectrolyte, bulk and local temperature, electrolyte flow rate, and thevelocity of electrolyte. For stainless steel and CoCr based alloys,phosphoric or chloride based solutions have worked well. For NickelTitanium alloys (Nitinol), sulfuric and LiCl based electrolytes haveshown promise with results. In general, the electrolysis/dissolution ofthe metal during the machining process should only take place upon theapplication of an applied overpotential to ensure adequate control overmachining characteristics. Thus the metal in the electrolyte is ideallyrendered passive in the absence of external power to drive thedissolution process.

In electrochemical machining, electrical contacts to the intravascularstent/implant 300 and the metal electrode 380 are made, with the stent300 being anode (+) and the metal electrode 380 being cathode (−). Inconventional electrochemical machining, the shape of tool electrodedefines the shape of workpiece product. Most of the machining takesplace on the front end of the electrode since there is a strongerelectrical field. However, as the tool machines into the workpiece,sidewalls of the tool also start facing the inner walls of theworkpiece. This introduces an extra portion of the current distribution.The defined channels are essentially the conductive pathways throughwhich dissolution will take place ion, which results in higher machiningrates in the entrance sides. One embodiment disclosed herein overcomesthis problem found in conventional machining by holding the anodicimplant 300 at a fixed distance from the cathodic electrode 380. Thisdistance is defined by the thickness of the non-conducting mask 340 onthe cathodic electrode 380. A fixed inter-electrode gap is maintained,thus avoiding the problem of higher machining rates on the entrancesides of the electrode. The amount of cathodic surface area exposed isdefined by the pattern to be transferred. Generally, it is good to startwith a 1:1 cathode/anode surface are ratio, where the anodic surfacearea is the working surface of the implant. Specifically in thisdisclosure, the working surface is the luminal surface of the implantand thus, the area used for ratio calculations is derived from thissurface only to avoid excessive current distributions.

The transfer accuracy of dimensional features from patterned electrodeto the implant is dictated largely by the depth/time of the machiningprocess relative to other feature dimensions targeted on the implant,like width. For example, if targeting 12 micron wide features on theimplant using a 2-3 micron machining depth/time to resolve, one maytarget very close to 12 micron wide features on the electrode to betransferred due to minimal under-cutting of the mask/implant interface.The degree to which undercutting occurs (isotropic machining) isresponsible for dimensional discrepancies that evolve over extendedmachining times. This is where the pulsing aspect attains the ideal cutsurface qualities, but also aids in implementing more directional(anisotropic) machining to minimize discrepancies between electrode andimplant pattern features. This is such that one achieves more of a 1:1pattern transfer.

With reference to FIG. 9, the shape of the electrode 380 may becircular, tubular, ellipsoidal, and the like. Preferably, the metalelectrode includes a circumference in the range of about 95% of thestent structure; more preferably, the metal electrode includes acircumference in the range of about 100% of the stent structure. Theelectrode 380 is disposed with its longitudinal axis being disposedsubstantially parallel with the longitudinal axis 316 of theintravascular stent 300.

Intravascular stents that are made of stainless steel are resistantagainst corrosion even upon moderate potentials, where its constituentsshould be dissolved from a thermodynamic perspective. In this passiveregion practically no electrochemical current is flowing; only at verypositive potentials, in the transpassive region, ion transport sets inand the steel is anodically dissolved. Specifically, for 1.4301stainless steel in 3 M HCl/₆M HF electrolyte, the passivation peak is ataround +0.2 V_(Pd/H) and the passive region extends to about +1.5V_(Pd/H). In micro-machining, highly concentrated NaCl electrolytes ormore ‘aggressive’ 3 M HCl/₆M HF electrolyte can be used for dissolutionof stainless steel at voltages of 10-40 V (low frequency AC) between thetool and the workpiece for pulse durations of 50-500 nanoseconds. Withsuch adjustment, electrochemical micromachining by ultrashort voltagepulses is applicable.

The embodiments disclosed herein, therefore, disclose a process for themass transfer or fabrication of micro-sized features on the innerdiameter of an intravascular stent via Electrochemical Micro-Machiningthrough an intravascular stent/metal electrode/non-conducting maskassembly.

Unlike other machining or pressing processes that impart micro-sizedfeatures one feature at a time, like directly writing micro-patternsonto the inner diameter using a laser, the fore-mentioned processimparts all desired features in one mass-transfer of the pattern, thushaving the potential to reduce process cycle times tremendously. Anotherappealing aspect of this process is that there are no stresses impartedto the surface which could otherwise result in compromised mechanicalperformance of the stent with respect to fatigue and crack initiation.In addition, the ECuM parameters could be strategically adjusted toproduce slightly rounded edges without the need for follow-upstress-relief processing.

While the present invention has been described with reference to itspreferred embodiments, those of ordinary skill in the art willunderstand and appreciate that variations in structural materials,bioactive agents, etching methods, device configuration or deviceindication and use may be made without departing from the invention,which is limited in scope only by the claims appended hereto.

We claim:
 1. A patterned masked electrode, comprising: a. An generallycylindrical electrically conductive electrode member having an outersurface; b. A non-conductive coating on the outer surface of theelectrode member; and c. A micro-pattern defined in the non-conductivecoating passing through the non-conductive coating and exposing definedportions of the electrode member.
 2. The patterned masked electrode ofclaim 1, wherein the non-conductive coating is of a material capable ofbeing vacuum deposited onto the outer surface of the electrode member.3. The patterned masked electrode method of claim 1, wherein themicro-pattern corresponds to a pattern of grooves adapted to betransferred to a luminal surface of an intraluminal stent.
 4. Thepatterned masked electrode of claim 3, further comprising anintraluminal stent concentrically engaged with the electrode member suchthat the non-conductive coating is intermediate the electrode member andthe intraluminal stent.
 5. The patterned masked electrode claim 1,wherein the non-conductive coating is made of a material capable ofbeing applied to the electrode member by one of dipping, spray coating,air brushing or lamination techniques.
 6. The patterned masked electrodeclaim 1, wherein the micro-pattern further comprises a plurality ofgrooves passing through the non-conductive coating, each of theplurality of grooves having a cross-sectional configuration selectedfrom the group consisting of square, u-shaped, triangular, v-shaped,rectangular, keyway shaped.
 7. An assembly, comprising: a. An generallycylindrical electrically conductive electrode member having an outersurface; b. A non-conductive coating on the outer surface of theelectrode member; c. A micro-pattern defined in the non-conductivecoating passing through the non-conductive coating and exposing definedportions of the electrode member; and d. An intraluminal stentconcentrically engaged around the non-conductive coating.
 8. Theassembly of claim 7, wherein the non-conductive coating is of a materialcapable of being vacuum deposited onto the outer surface of theelectrode member.
 9. The assembly of claim 7, wherein the micro-patterncorresponds to a pattern of grooves adapted to be transferred to aluminal surface of an intraluminal stent.
 10. The assembly of claim 7,wherein the non-conductive coating is made of a material capable ofbeing applied to the electrode member by one of dipping, spray coating,air brushing or lamination techniques.
 11. The assembly of claim 7,wherein the micro-pattern further comprises a plurality of groovespassing through the non-conductive coating, each of the plurality ofgrooves having a cross-sectional configuration selected from the groupconsisting of square, u-shaped, triangular, v-shaped, rectangular,keyway shaped.